Immune complexes are the most common cause of human glomerulonephritis. Animal studies have established that the administration of excess antigen dissolves glomerular immune complex deposits. The objective of this proposal is to examine in experimental models the feasibility of applying this principle as a therapeutic modality in treating immune complex glomerulonephritis. The passive administration of preformed complexes produces glomerular immune complex deposits in mice. The administration of excess antigen causes the dissolution of these deposits. The possiblity that antigen fragments can also remove these deposits will be explored since likely antigen fragments are less likely to produce untoward reactions. The information derived from the above experiments will be applied to a chronic form of experimental immune complex disease. Glomerulonephritis will be induced by various regimens of chronic antigen administration, and the lesions will be characterized. The effect of administering excess antigen and antigen fragments on the subsequent course of the glomerulonephritis and on the endogenous immune response will be studied. The possibility that various regimens of administering antigen or antigen fragments could ameliorate the disease process by inducing immunologic tolerance will be pursued. Finally, the above principles will be applied to the spontaneous glomerulonephritis of NZB/W mice. The immune complexes comprising the glomerular desposits are composed predominatly of nuclear antigens and antibodies to these antigens. Large doses of single-stranded DNA or its fragments will be administered to these mice in an attempt to cause dissolution of the glomerular deposit, and the influence of this regimen upon the subsequent disease course will be determined. If these experiments are successful, the derived principles could possibly provide a new therapeutic approach to human immune complex-induced glomerulonephritis.